Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome (EVAMP)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by (Responsible Party):
Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01178151
First received: July 26, 2010
Last updated: July 1, 2014
Last verified: July 2014

July 26, 2010
July 1, 2014
October 2010
September 2014   (final data collection date for primary outcome measure)
To determine the response rate of Everolimus in patients with advanced cancer and PJS. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
Same as current
Complete list of historical versions of study NCT01178151 on ClinicalTrials.gov Archive Site
  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies [ Time Frame: avarage of 18 months ] [ Designated as safety issue: No ]
    The time between date of entering the study and date of death will be collected.
  • To determine the time to progression of PJS patients treated with everolimus for advanced malignancies. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
  • To determine the safety and toxicity of Everolimus in this patient population [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events determined by the CTCAE 4.0 as a Measure of Safety and Tolerability
  • To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    Drug trough levels will be taken once every 3 weeks and stored frozen until measurement at the end of the study
  • To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and collected specimens during treatment and correlate with response to treatment. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    All patients who are willing to undergo extra tissue collection will have a tumor and where possible a polyp biopsy before treatment and for tumor biopsy in week 2 and 4 and for polyps once every 6 months during treatment for biomarker investigations. The activity of mTOR and its downstream targets will be measured in the tumor as well as the arborization pattern and apoptosis activity in the polyps.
  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies [ Time Frame: Conclusion of the study, expected avarage of 18 months ] [ Designated as safety issue: No ]
    The time between date of entering the study and date of death will be collected.
  • To determine the time to progression of PJS patients treated with everolimus for advanced malignancies. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
  • To determine the safety and toxicity of Everolimus in this patient population [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events determined by the CTCAE 4.0 as a Measure of Safety and Tolerability
  • To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    Drug trough levels will be taken once every 3 weeks and stored frozen until measurement at the end of the study
  • To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and collected specimens during treatment and correlate with response to treatment. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    All patients who are willing to undergo extra tissue collection will have a tumor and where possible a polyp biopsy before treatment and for tumor biopsy in week 2 and 4 and for polyps once every 6 months during treatment for biomarker investigations. The activity of mTOR and its downstream targets will be measured in the tumor as well as the arborization pattern and apoptosis activity in the polyps.
Not Provided
Not Provided
 
Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
Pilot Study of Everolimus in the Treatment of Neoplasms in Patients With Peutz-Jeghers Syndrome

In this pilot study the investigators will treat all patients known with Peutz-Jeghers syndrome (PJS) who are diagnosed with advanced malignancies with everolimus 10mg daily until disease progression. Most patients with PJS have an inherited LKB1 mutation leading to aberrant m-TOR activity. Their risk to develop malignancies or intestinal polyps is probably related to this constitutive mTOR signaling. The hypothesis is that mTOR inhibition is an effective anticancer treatment in PJS patients with advanced malignancies.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Peutz-Jeghers Syndrome
  • Neoplastic Processes
  • Neoplasm Metastasis
Drug: Everolimus
10mg daily orally
Other Name: Afinitor, RAD001, everolimus
Experimental: afinitor
10mg afinitor daily orally
Intervention: Drug: Everolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
September 2014
September 2014   (final data collection date for primary outcome measure)

Tow cohorts of PJS patients will be included. Cohort 1: Advanced malignancy Cohort 2: High risk polyps

General inclusion criteria:

  1. Known Peutz-Jeghers disease (with LKB1 mutation)
  2. No concurrent systemic anti cancer treatment
  3. No prior treatment with m-TOR inhibitor
  4. Prior malignancies or concurrent second malignancies are allowed
  5. Prior systemic therapy is permitted with a washout time of at least 4 weeks
  6. ECOG/ WHO performance 0-2
  7. Age > 18 years
  8. Adequate renal function (defined as creatinine < 150 μmol/L)
  9. Adequate liver function (bilirubin < 1.5 times upper limit of normal, ALAT or ASAT < 5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit of normal in absence of liver metastases
  10. Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)
  11. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  12. No pregnancy or lactating and ifof childbearing potential patients must agree to use a reliable contraceptive method throughout the study
  13. No serious concomitant systemic disorder that would compromise the safety of the patient,at the discretion of the investigator
  14. Signed informed consent according to ICH/GCP.
  15. No uncontrolled symptomatic hyperglycaemia

Specific inclusion criteria for cohort 1:

  1. Cytological or histological confirmed carcinoma
  2. Metastatic or non-resectable disease
  3. Patients with clinically and/or radiographically documented measurable lesion according to

RECIST criteria:

  1. X-ray, physical exam > 20 mm
  2. Spiral CT scan > 10 mm
  3. Non-spiral CT scan > 20 mm

Specific inclusion criteria for cohort 2:

  1. Known high risk polyps (definition see page 19)
  2. Ability to undergo endoscopies

Specific Exclusion criteria:

Symptomatic PJ-polyps, defined as polyps likely to be responsible/causal for the abdominal symptoms the patient presents with.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01178151
AMCmedonc010, 2010-020451-32
Yes
Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Principal Investigator: Heinz-Josef Klumpen, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP